Polymerizable cyanoacrylate monomer formulations have been disclosed for a variety of topical uses. Specifically, such formulations have been used as an alternate or an adjunct to surgical sutures and/or staples in wound closure, by forming a polymeric film over the approximated edges of a wound or an incision. Antimicrobial agents may be incorporated into cyanoacrylate monomer formulations in an effort to improve the microbial barrier properties of the resultant polymeric film. However, it is critical that the antimicrobial agent does not cause premature polymerization of the cyanoacrylate monomer formulation when it is desirable for the formulation to be stable over extended periods of time, for use at a later date, i.e., polymerization at a later date. Additionally, the antimicrobial agent must not interfere with the polymerization when the cyanoacrylate monomer formulation is applied to, for example, the approximated edges of a wound. Additionally, the antimicrobial agent must not have any detrimental effect to the mechanical strength of the cyanoacrylate monomer formulation. Finally, the antimicrobial agent must be capable of being released from the polymeric film in sufficient amounts for the agent to be effective.
In this regard, U.S. Pat. No. 6,214,332 describes the compatibility of cyanoacrylate monomers with various antimicrobial agents, such as polyvinylpyrollidone-iodine, silver nitrate, hexachlorophene, merbromin, tetracycline-HCl, tetracycline hydrate and erythromycin. This reference indicates that polyvinylpyrollidone-iodine in solid form produces a cyanoacrylate monomer formulation that is stable for 8 weeks when stored at room temperature, polymerizes to form a polymeric film within 30 seconds, and exhibits an antimicrobial effect.
However, many conventional antimicrobial agents are unsuitable for use in cyanoacrylate monomer formulations due to their inability to satisfy one or more of the criteria described above. For example, although quaternary ammonium salts are commonly used antimicrobial agents, they are also known to initiate polymerization of cyanoacrylate monomers, as described in U.S. patent application Ser. No. 2003/0007948 A, as well as U.S. Pat. Nos. 5,928,611 and 6,767,552. Therefore, it is undesirable to use a quaternary ammonium salt as an antimicrobial agent in a cyanoacrylate monomer formulation when the formulation is required to be stable over extended periods of time.
The use of diiodomethyl-p-tolylsulfone as an antimicrobial agent is desirable because it is a broad spectrum antimicrobial agent. For example, blends of diiodomethyl-p-tolylsulfone, such as Amical-48 (commercially available from Dow), and acrylic hot melt adhesive polymers have been reported in U.S. Pat. No. 6,216,699, for use in surgical incise drapes having antimicrobial properties. Such blends were reported to indicate zones of inhibition against several organisms including S. aureus, E. coli, P. aeruginosa, K. pneumoniae, P. cepacia, E. cloacae, S. marcescens, S. pyogenes, E. faecalis-Vancomycin Resistant, C. albicans and B. subtilis. However, use of diiodomethyl-p-tolylsulfone in a formed polymer or by direct mixing in the polymer melt does not ensure that diiodomethyl-p-tolylsulfone is suitable for use with prepolymeric compositions such the cyanoacrylate monomer formulations described herein.
Therefore, it is desirable to have a stable formulation of cyanoacrylate monomer and diiodomethyl-p-tolylsulfone, where the diiodomethyl-p-tolylsulfone does not cause premature polymerization of the cyanoacrylate monomer formulation when it is desirable for the formulation to be stable over extended periods of time, for use at a later date, i.e., polymerization at a later date; the diiodomethyl-p-tolylsulfone does not interfere with the polymerization when the cyanoacrylate monomer formulation is applied to, for example, the approximated edges of a wound; and the diiodomethyl-p-tolylsulfone is capable of being released from the polymeric film in sufficient amounts to be effective.